Since the late 1700's, when Edward Jenner observed that individuals that had been inoculated with cowpox exhibited subsequent immunity to a smallpox challenge, it has been known to confer resistance to disease by vaccination. The basic principle behind the practice of immunization is that the body's own immune system is stimulated to produce a humoral or cellular response against a specific disease-causing organism by exposing the system to an antigen of the causative agent without actually bringing on the full symptoms of the disease. With the humoral and/or cellular response thus elicited, the treated individual is then protected against a future exposure to the virulent pathogen.
Although the principle is a relatively simple one, the difficulties associated with the development of a vaccine which is both safe and effective are many. First, it must be ensured that the stimulatory antigen is no longer capable of causing the disease with which it is associated, or at most only causes subclinical symptoms. Some commonly employed methods of achieving this include: using killed or inactivated organisms (U.S. Pat. Nos. 3,975,517; 4,152,414), inactivating the specific toxin which causes symptoms (U.S. Pat. Nos. 4,029,765; 4,007,265), or in some manner reducing or eliminating the virulence of the living organism to be used in the vaccine (U.S. Pat. Nos. 3,944,469; 4,110,433). Each of these methods presents certain difficulties in that the procedure required may be costly and time consuming; the inactivation may also adversely affect the antigenicity of the toxin, or the avirulent organism may revert back to its virulent state once in the body. Another problem involved with vaccine preparation is providing an amount of antigen sufficient, or for a long enough period of exposure, to elicit the desired immune response. This can be difficult when using certain types of very expensive antigens, which are not only costly to produce in large amounts, but are also rapidly eliminated from the body when provided as a vaccine in the traditional manner. In order to augment the immunogenicity of certain types of antigen, they are often combined with adjuvants which will enhance antibody production (U.S. Pat. No. 4,152,423; 4,001,395; 4,094,971). These substances may not only be difficult and time-consuming to prepare, but also may act as irritants when injected, causing vaccination to be quite painful.
There has now been discovered a method of preparing vaccines which can solve one or both of the above problems. Observations made in connection with the present invention show that linking an antigen to an insoluble support or carrier can serve to increase the power of the antigen to induce antibody formation while at the same time prolonging the lifetime of the antigen in the body. This means that the amount of antigen required is lessened and reduces the need for repeated exposures. It has also been unexpectedly discovered that certain toxins may be used safely in this form without prior inactivation, thereby eliminating the need for chemical treatment which may also severely compromise the toxin's antigenicity.